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According to the World Health Organization, the number of people worldwide afflicted with Alzheimer’s disease will rise from 24 million people today to 42 million in 2020 and to 81 million in 2040.

And most of these new cases will occur in developed, affluent countries, whose sedentary lifestyles and nutrition-poor, calorie-rich diets appear to promote the disease.

The immediate causes of the brain cell (neuron) damage that produces Alzheimer’s disease—amyloid protein plaque and “tangles” made of tau protein—appear pretty clear.

But the silent forces driving these processes have been a mystery… until now, if new research results prove correct.Let’s take a look at two related studies, both published in recent weeks.The first—from Northwestern University—suggests that inadequate blood flow to the brain promotes buildup of the protein plaque that leads to Alzheimer’s.

Drawing on studies in humans and mice, researchers from Northwestern University have demonstrated that a gradual reduction in blood flow to the brain could be a major initiator of the brain changes that characterize Alzheimer's disease (O'Connor T et al. 2008).It appears that a poor supply of blood sugar (glucose) to brain cells triggers a biochemical chain reaction that results in the accumulation of an enzyme that promotes build up of amyloid protein that kill off brain cells.As lead author Robert Vassar, Ph.D. said, “This finding is significant because it suggests that improving blood flow to the brain might be an effective therapeutic approach to prevent or treat Alzheimer's. If people start early enough, maybe they can dodge the bullet” (NWU 2008).Sugar-shortage triggers chain reaction that mimics strokesTen years ago, Dr. Vassar discovered that an enzyme called BACE1 produces sticky clumps of amyloid protein that form outside neurons and disrupt their ability to send messages.Vassar’s study shows that energy (glucose) deprivation in the brain might be the trigger starting the process that forms plaques in Alzheimer’s.Drawing from experiments with humans and mice, Vassar and colleagues showed that reduced blood flow alters a protein called elF2alpha.In its changed form, elF2alpha increases the output of the BACE1 enzyme, which spurs production of amyloid beta protein outside neurons and disrupts their ability to send messages.Vassar said his work suggests that Alzheimer’s disease may result from a less severe type of energy deprivation than occurs in a stroke.Rather than dying, as in a stroke, the brain cells react by increasing BACE1, which may be a protective response in the short term but is harmful in the long term.“A stroke is a blockage that prevents blood flow and produces cell death in an acute, dramatic event,” Vassar said. “What we are talking about here is a slow, insidious process over many years where people have a low level of cardiovascular disease or atherosclerosis in the brain. It's so mild, they don't even notice it, but it has an effect over time because it's producing a chronic reduction in the blood flow” (NWU 2008).Vassar said when people reach a certain age, some may get increased levels of the enzymes that cause a build-up of the plaques: “Then they start falling off the cliff” (NWU 2008).He says that people can improve blood flow through exercise, reducing cholesterol levels, and lowering blood pressure.Ideally, Professor Vassar would have noted that, in animal studies, dietary omega-3s boost the rate of glucose uptake by brain cells, by raising brain levels of two essential glucose-transport proteins (Pifferi F et al. 2005 and 2007).In other words, diets rich in omega-3s probably cause human brain cells to absorb a greater proportion of the glucose carried by the brain’s blood supply (See “Feel-Good Findings: Omega-3s Boost Mood, Reduce Anger, Ensure Brain’s Flow of Fuel”).In addition, population studies suggest that dietary antioxidants from colorful fruits and vegetables are shown to reduce the risk of Alzheimer’s (See “Alzheimer’s Risk Curbed by Antioxidants in Fruit and Vegetable Juice”).The study co-author’s advice to lower blood cholesterol levels applies particularly—and perhaps only—to the one in five Americans who share the APOE4 gene. People who carry this gene are much more likely to develop the brain abnormalities characteristic of Alzheimer’s disease, and develop symptoms of Alzheimer’s (See “Fast Food Diet May Raise Alzheimer’s Risk”).

“If people start early enough, maybe they can dodge the bullet,” Vassar said. For people who already have symptoms, vasodilators, which increase blood flow, may help the delivery of oxygen and glucose to the brain, he added (NWU 2008).It also is possible that drugs could be designed to block the eIF2alpha protein that begins the formation of amyloid plaques.Study #2 (Tufts University)—Do low-carb diets fog brains?

The Northwestern University team’s findings suggest that low-carb diets could be damaging to brain over the long term.And indeed, new study from Tufts University found that when dieters eliminated carbohydrates from their meals, they performed more poorly on memory tasks than when they reduced their total calorie intake but not their intake of carbohydrates (D'Anci KE et al. 2008).When their carbohydrate intake was restored to prior levels, their cognition skills returned to normal.“This study demonstrates that the food you eat can have an immediate impact on cognitive behavior,” said lead author Holly A. Taylor, Ph.D. “The popular low-carb, no-carb diets have the strongest potential for negative impact on thinking and cognition” (TU 2008).While the brain uses glucose as its primary fuel, it has no way of storing it. Rather, the body breaks down carbohydrates into glucose, which is carried to the brain through the blood stream and used immediately by nerve cells for energy.Reduced carbohydrate intake should thus reduce the brain’s source of energy.Study participants included 19 women ages 22 to 55 who were allowed to select the diet plan they preferred… either a low-carbohydrate diet or a low-calorie, macronutrient balanced diet.Nine women chose a low-carbohydrate diet and 10 selected the low-calorie diet.The 19 dieters completed five testing sessions that assessed cognitive skills, including attention, long-term and short-term memory, and visual attention, and spatial memory.The first session was held before participants began their diets, the next two sessions occurred during the first week of the diet, which corresponded to the week when low-carb dieters eliminated carbohydrates.The final two sessions occurred in week two and week three of the diets, after carbohydrates had been reintroduced for those on the low-carb diet.The results suggest that low-carb diets may impair memory and reaction time:

Low-carb dieters showed a gradual decrease on the memory-related tasks compared with the low-calorie dieters.

Reaction time for those on the low-carb diet was slower and their visuospatial memory was not as good as those on the low-calorie diet.

The Tufts researchers noted that—consistent with the results in this study—past studies have shown that diets high in protein or fat can improve a person's attention in the short-term (Halyburton AK et al. 2008).

“Although the study had a modest sample size, the results showed a clear difference in cognitive performance as a function of diet,” said Taylor (TU 2008).The conclusion we’d draw with regard to the effect of diet on brain performance is that neither very-low-carb nor very-low-fat diets seem ideal.As in all things dietary, a balanced approach appears best.Participants were also asked about their hunger levels and mood during each session.The hunger-rating did not vary between participants on a low-carb diet and those on a low-calorie diet.The only mood difference between dieters was confusion, which was higher for low-calorie dieters during the middle of the study.“Although this study only tracked dieting participants for three weeks, the data suggest that diets can affect more than just weight,” said Taylor. “The brain needs glucose for energy and diets low in carbohydrates can be detrimental to learning, memory, and thinking” (TU 2008).One factor not mentioned by the Tufts team is the role that different kinds of dietary fat play in brain health.There is little doubt that omega-3s are essential to optimal brain health, and that for people with the APOE4 gene, high blood cholesterol levels can harm blood vessels in the brain.